Distinct B-Cell Specific Transcriptional Contexts of the BCL2 Oncogene Impact Pre-Malignant Development in Mouse Models.

Upregulated expression of the anti-apoptotic oncogene is a common feature of various types of B-cell malignancies, from lymphoma to leukemia or myeloma. It is currently unclear how the various patterns of deregulation observed in pathology eventually impact the phenotype of malignant B cells and their microenvironment. Follicular lymphoma (FL) is the most common non-Hodgkin lymphoma arising from malignant germinal center (GC) B-cells, and its major hallmark is the t(14:18) translocation occurring in B cell progenitors and placing the gene under the control of the immunoglobulin heavy chain locus regulatory region (IgH 3'RR), thus exposing it to constitutive expression and hypermutation.

Azacitidine Omega-3 Self-Assemblies: Synthesis, Characterization, and Potent Applications for Myelodysplastic Syndromes.

5-Azacitidine, a cytidine analogue used as a hypomethylating agent, is one of the main drugs for the treatment of myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) in the elderly. However, after administration, it exhibits several limitations, including restricted diffusion and cellular internalization due to its hydrophilicity, and a rapid enzymatic degradation by adenosine deaminase. The aim of this study was to improve the drug cell diffusion and protect it from metabolic degradation via the synthesis of amphiphilic prodrugs and their potential self-assembly.

Therapeutic perspective of thiosemicarbazones derivatives in inflammatory pathologies: A summary of in vitro/in vivo studies.

Following induction of inflammation, the nuclear factor kappa B (NF-κB) in activated macrophages induces the transcription of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and cyclooxygenase (COX), an inflammatory enzyme implicated in the synthesis of prostaglandins (PGs). The latter are involved in the transition and the maintenance of chronic inflammation underling various chronic disorders that require treatment. Concerning this, many anti-inflammatory drugs are available to treat the inflammatory disorders, but their therapeutic use is associated with a variety of side effects.

Bromodomain and extraterminal (BET) protein inhibition of IgG/IgE production in murine B cells is counter-balanced by a strong Th2 bias.

Objectives: Inhibitors of bromodomain and extra terminal domain (BET) proteins are a new and growing class of anti-cancer drugs, which decrease oncogene expression by targeting superenhancers. Antibody production is another physiological process relying on superenhancers, and it remains to be clarified whether potential immunomodulatory properties of BET inhibitors might impact humoral immunity and allergy.

Methods: We thus evaluated humoral immune responses and their Th2 context and in mice following treatment with the classical BET-inhibitor JQ1.

The evolution of nucleosidic analogues: self-assembly of prodrugs into nanoparticles for cancer drug delivery.

Nucleoside and nucleotide analogs are essential tools in our limited arsenal in the fight against cancer. However, these structures face severe drawbacks such as rapid plasma degradation or hydrophilicity, limiting their clinical application. Here, different aspects of nucleoside and nucleotide analogs have been exposed, while providing their shortcomings.

Apolipoprotein C-III and cardiovascular diseases: when genetics meet molecular pathologies.

Cardiovascular diseases (CVD) have overtaken infectious diseases and are currently the world's top killer. A quite strong linkage between this type of ailments and elevated plasma levels of triglycerides (TG) has been always noticed. Notably, this risk factor is mired in deep confusion, since its role in atherosclerosis is uncertain.

Mesangial Deposition Can Strongly Involve Innate-Like IgA Molecules Lacking Affinity Maturation.

Background: IgA nephropathy (IgAN) often follows infections and features IgA mesangial deposition. Polymeric IgA deposits in the mesangium seem to have varied pathogenic potential, but understanding their pathogenicity remains a challenge. Most mesangial IgA1 in human IgAN has a hypogalactosylated hinge region, but it is unclear whether this is required for IgA deposition.

Chemical Composition, Antioxidant and Anti-inflammatory Activity Evaluation of the Lebanese Propolis Extract.

Background: Propolis is a resinous substance produced by bees and known to possess antioxidant, antimicrobial, antiproliferative and anti-inflammatory activities.

Objective: This study is aimed at evaluating the in vivo and in vitro anti-inflammatory potential of the Crude Ethanolic Extract (CE) of Lebanese propolis and its Ethyl Acetate Fraction (EAF).

Method: Chemical content of propolis was characterized using high-performance liquid chromatography and LC-MS/MS.

Apoliporotein L3 interferes with endothelial tube formation via regulation of ERK1/2, FAK and Akt signaling pathway.

Background And Aims: Endothelial cells are main actors in vascular homeostasis as they regulate vascular pressure and permeability as well as hemostasis and inflammation. Disturbed stimuli delivered to and by endothelial cells correlate with the so-called endothelial dysfunction and disrupt this homeostasis. As constituents of the inner layer of blood vessels, endothelial cells are also involved in angiogenesis.

Myeloperoxidase promotes tube formation, triggers ERK1/2 and Akt pathways and is expressed endogenously in endothelial cells.

Myeloperoxidase is a member of the mammalian peroxidase family, mainly expressed in the myeloblastic cell lineage. It is considered a major bactericidal agent as it is released in the phagosome where it catalyzes the formation of reactive oxygen species. It is also released in the extracellular spaces including blood where it is absorbed on (lipo)proteins and endothelial cell surface, interfering with endothelial function.

Chemical Composition and Antioxidant, Anti-Inflammatory, and Antiproliferative Activities of Lebanese Ephedra Campylopoda Plant.

Background: This study aimed to identify the phytochemical content and evaluate the antioxidant, anti-inflammatory, and antiproliferative capacities of various solvent extracts of stems.

Material/methods: Fresh stems were suspended in 3 different solvent systems, including distilled water, ethanol, and methanol The chemical composition was determined using high-performance liquid chromatography (HPLC), and the content of essential oil of this plant species was determined by gas chromatography (GC) coupled with mass spectrometry (MS). Antioxidant activity was determined using DPPH radical scavenging and Fe-chelating activity assays.

Chemical characterization and cytotoxic activity evaluation of Lebanese propolis.

Chemical composition, anti-proliferative and proapoptotic activity as well as the effect of various fractions of Lebanese propolis on the cell cycle distribution were evaluated on Jurkat leukemic T-cells, glioblastoma U251 cells, and breast adenocarcinoma MDA-MB-231 cells using cytotoxic assays, flow cytometry as well as western blot analysis. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed that ferulic acid, chrysin, pinocembrin, galangin are major constituents of the ethanolic crude extract of the Lebanese propolis, while the hexane fraction mostly contains chrysin, pinocembrin, galangin but at similar levels. Furthermore chemical analysis was performed using gas chromatography-mass spectrometry (GC-MS) to identify major compounds in the hexane fraction.

Chemical Composition, Antioxidant, Anti-Inflammatory, and Antiproliferative Activities of the Plant Lebanese Crataegus Azarolus L.

BACKGROUND In the present study, phytochemical screening, antioxidant, anti-inflammatory, and antiproliferative capacities of 3 extracts from leaves of Lebanese Crataegus azarolus L. were evaluated. MATERIAL AND METHODS Fresh leaves were dissolved in 3 different solvents: distilled water, ethanol, and methanol.